摘要:

We have studied the effect of superior spermatic nerve (SSN) section on testicular gonadotropin receptors and in vitro androgen production by immature rat testis. Bilateral testicular denervation had no effect on testicular weight, serum androgens, LH, FSH and PRL levels. Denervation resulted in a significant inhibition of hCG stimulated in vitro androgen production. A reduction in the number of testicular LH receptors was observed after SSN section, while FSH binding sites remained unchanged. These results indicate that the number of LH receptors and testicular steroidogenic response to hCG are influenced by nerves reaching the testis.

ISSN:0028-3835    

DOI:10.1159/000126359

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effects of the α2-agonist clonidine (CLO), the serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (5-HTP), the 5-HT2/histamine (H1) antagonist cyproheptadine (CYPRO), the muscarinic cholinergic antagonist atropine (ATR), and an affinity-purified polyclonal anti-rat growth hormone-releasing hormone (rGHRH) immunoglobulin on serum concentrations of growth hormone (GH) and prolactin (PRL) were tested in 2- and 10-day-old litter-mate rat pups. Serum levels of GH and PRL were detected in RIA and Nb2 lymphoma bioassay, respectively. The effects of two different drugs either alone or in combination with each other were evaluated by two-factor analysis of variance. The data indicated that secretion of GH and PRL was regulated by α2-adrenergic, serotonergic and cholinergic mechanisms; the pathways regulating the two hormones, however, were distinct. 5-HTP stimulated GH secretion as early as day 2 postpartum via cholinergic mechanisms not involving GHRH; this pathway was also present in 10-day-old pups. An additional serotonergic pathway was functional in 10-day-old pups which mediated CLO-induced release of GH, and did not include cholinergic transmission. The α2-adrenergic regulation of GH secretion appeared to involve three distinct mechanisms: (1) a sexually uniform GH-stimulating α2-adrenergic pathway was demonstrated with CLO in 2-day-old pups only after pretreatment with ATR; (2) a sexually dimorphic CLO-induced secretion of GH was observed that was mediated by mechanisms sensitive to CYPRO but not to ATR, and occurred by day 10; and (3) 5-HTP-induced GH secretion was counteracted by CLO in 10-day-old pups of both sexes indicating that a sexually uniform GH-inhibiting α2-adrenergic pathway was present. The concentration of PRL was not affected by 5-HTP up to day 10, and was decreased by ATR in 10-day-old (but not in 2-day-old) pups. Secretion of GH and PRL appeared to be stimulated by different sets of cholinergic neurons because (1) ATR inhibited GH secretion on day 2 but inhibition of PRL secretion appeared later, and (2) CLO-induced PRL secretion was diminished by ATR, whereas CLO-induced release of GH was not affected in 10-day-old pups. CYPRO increased serum levels of PRL in 10-day-old pups; thus, PRL-inhibiting network was functional at this age. Whether the inhibition of this pathway was due to the serotonin, histamine (H1) or dopamine antagonist action of CYPRO requires further investiga

ISSN:0028-3835    

DOI:10.1159/000126360

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Prolonged maternal deprivation during early ontogeny results in increased basal and stress-induced corticosterone levels. In the following experiments we examined whether these increases were due, at least in part, to augmented ACTH secretion. Thus, ACTH levels were measured in 24-hour maternally deprived and nondeprived 6-, 9-, and 12-day-old pups exposed to a mild stressor (i.e. saline injection followed by placement in a novel environment at room temperature). The results showed: (1) nondeprived pups showed a small response to saline – the response of deprived pups, however, was greater than that of nondeprived pups; (2) the magnitude of the response increased with age; (3) ACTH levels remained elevated for at least 30 min. Subsequent experiments examined whether the continuous exposure to novelty and/or loss of body heat could explain the persistence of this response. Neither variable affected the ACTH response to saline. Our results indicate that factors of maternal origin are partly responsible for the regulation of the ACTH response to stress. Furthermore, the persistence of the response suggests that the negative feedback system in the infant is immatur

ISSN:0028-3835    

DOI:10.1159/000126361

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The developmental and sex-related changes in the hypothalamic-pituitary GH axis were examined in lean and obese Zucker male and female rats from 6 to 12 weeks of age. Pituitary GH content was not different in any phenotype/sex group at 6 weeks. GH content increased with age in male rats, but at 10 and 12 weeks content was decreased in obese male rats relative to lean rats. GH content did not increase in female rats and there was no difference in content between lean and obese female rats. Hypothalamic GHRH content was not different between the groups. Hypothalamic SS content was decreased in obese male rats compared to lean male rats (95%) and in obese female rats compared to lean female rats (78%). Individual 6-hour plasma GH profiles from rats 6-7 weeks of age showed the characteristic sexually dimorphic GH secretory patterns. However, spontaneous GH secretion was dramatically reduced in obese animals when compared to sex-matched lean rats. GH peak amplitude (25% of lean) and mean GH concentration (19% of lean) were decreased in obese male rats without a significant alteration in GH peak frequency or baseline level. In obese female rats, the number of GH peaks, peak amplitude, baseline GH, and mean GH concentration were all decreased compared to lean. The reduction in peak amplitude (14% of lean) and in mean GH concentration (20% of lean) was similar to the reduction in obese male rats. Serum IGF-I concentrations were not different among the groups at 6 weeks. IGF-I levels in male rats increased with age but were not different between lean and obese rats. IGF-I concentrations in female rats were unchanged with time and were not different between lean and obese rats. Serum insulin was increased in obese male and female rats at 6 through 12 weeks. We conclude (1) GH secretion is depressed at 6-7 weeks in obese male and female rats with the magnitude of reduction similar to previous observations in male rats 12 weeks or older; (2) pituitary GH content is depressed only in obese male rats and occurs after the defect in GH secretion; (3) hypothalamic GHRH content is unchanged and hypothalamic SS is slightly to moderately decreased in obese rats; (4) serum IGF-I is not different between lean and obese rats; (5) obese male and female rats were hyperinsulinemic. These observations suggest that decreases in GH secretion occur at or before 6-7 weeks and that some previously observed changes in the GH axis occur secondarily after impaired GH secretion. The search for the mechanism of decreased GH secretion should examine the GH axis early in development on or before 6-7 weeks.

ISSN:0028-3835    

DOI:10.1159/000126362

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Previous neuroanatomical studies have revealed a localization of galanin in several nuclei in the brain stem which are involved in the hemodynamic control of arginine vasopressin (AVP) release. The present study, therefore, investigates the contribution of endogenous galanin to the plasma volume-mediated control of AVP release in conscious rats. Injection of synthetic rat galanin (12.5-50 pmol/rat) into the cisterna magna (i.c.s.) suppressed plasma AVP increased by polyethylene glycolinduced hypovolemia (2.45 ± 0.24 pg/ml at 50 pmol/rat vs. the vehicle group 5.72 ± 0.69 pg/ml, p < 0.01). In contrast, when plasma AVP was suppressed by isotonic plasma volume expansion, immunoneutralization of endogenous galanin by antigalanin-antibody i.c.s. significantly reversed the suppression (1.02 ± 0.07 pg/ml vs. vehicle group 0.63 ± 0.05 pg/ml, p < 0.01) without altering the mean arterial blood pressure. These results suggest that endogenous galanin is physiologically involved in the plasma volume-mediated control of AVP release through an inhibitory action on this path

ISSN:0028-3835    

DOI:10.1159/000126363

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Thymosin fraction five (TF5), a well-characterized immunoregulatory thymic preparation, has been reported to stimulate corticotropin (ACTH) release from rat pituitary cells. Since a previous study in our laboratory had shown that TF5 was able to stimulate ACTH release from corticotropin-releasing hormone (CRH)-insensitive corticotropic tumor cells, it was of interest to assess the role of calcium in the mechanism of action of TF5 on corticotropic cells. A CRH-insensitive variant, denoted AtT-20(CI), of the wild-type corticotropic tumor cell line AtT-20 was used. Synthetic h/rCRH within a dose range of 0.1-100 nM was completely ineffective to stimulate basal ACTH release from AtT-20(CI) cells, although the same batch of neuropeptide displayed the expected ACTH-releasing activity on dispersed rat pituitary cells (for instance, 0.1 nM CRH induced a 3.7-fold increase in ACTH release in this cell system). Median eminence extracts (1/10) induced only a 12% increase in ACTH release from AtT-20(CI) cells as compared to the 395% stimulation induced in normal pituitary cells. As expected, TF5 induced a dose-dependent increase in ACTH release from AtT-20(CI) cells. However, this ACTH-releasing activity of TF5 was completely abolished when cells were incubated in Ca-free medium or Ca-free medium containing 0.5 mM EGTA. On the other hand, the presence of the Ca ionophore A23187 (5 µM) in medium containing normal Ca levels (2.5 mM) did not affect the ACTH-releasing activity of TF5 on AtT-20(CI) cells. Our results suggest that thymosin peptides exert their ACTH-releasing effect on corticotrophs by a Ca-dependent mechanism which does not require the integrity of the CRH receptor-associated activation pathway

ISSN:0028-3835    

DOI:10.1159/000126364

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Corticotropin-releasing factor (CRF) is a potent factor involved in the antireproductive effects of various stressors. However, the central mechanisms by which CRF modulates the hypothalamic-pituitary-gonadal (HPG) axis are not well understood. In order to verify whether CRF is able to directly influence luteinizing hormone-releasing hormone (LHRH) secretory activity at the level of the medial preoptic area (MPOA), CRF was chronically or acutely injected bilaterally into this hypothalamic area. Ten days before the experiments, female rats were implanted with a permanent double-guide cannula which was stereotaxically positioned close to the MPOA. Chronic administration of rat CRF (rCRF) was accomplished by means of two miniosmotic pumps connected to double internal cannula. Acute bilateral infusion of rCRF into the MPOA was performed in unrestrained ovariectomized (OVX) rats and during the afternoon of proestrus. Ten minutes before rCRF treatment, antagonists of opioid receptors (µ, µι, or k) were infused bilaterally into the MPOA. Hypothalamic LHRH release as well as circulating gonadotropins were determined using a push-pull cannula implanted into the median eminence (ME), and a catheter connected to the jugular vein, respectively. Chronic rCRF treatment in the MPOA decreased (p < 0.05) plasma LH levels but did not modify follicle-stimulating hormone release in OVX rats. A significant inhibition of LH secretion was first observed 80 min after the acute rCRF infusion into the MPOA; pretreatment with nor-Binaltorphimine (antagonist of K-receptors) did not measurably attenuate this effect. In contrast, bilateral administration of β-Funaltrexamine (antagonist of µ-opioid receptors) or naloxonazine (µ1-antagonist) partially attenuated the inhibitory effect of rCRF on plasma LH levels. Similarly, injections of rCRF bilaterally into the MPOA suppressed hypothalamic LHRH release into the ME and this effect was partially reversed by a previous administration of opioid µ- or µ1-receptor antagonists. In contrast to rCRF injection into the MPOA, administration of rCRF into the paraventricular nucleus the arcuate nucleus of the hypothalamus and directly into the ME were without significant effect on hypothalamic LHRH release in proestrus rats. In conclusion, the present data show that from among the hypothalamic sites tested, only the MPOA proved susceptible to CRF-induced alteration of LHRH neuronal activity during proestrus afternoon in rats. The release of opioids from nerve terminals located in the MPOA, which in turn binds and activates mainly type µi-receptors, might contribute to this inhibitory influence of CRF on LHRH release in the infundibula

ISSN:0028-3835    

DOI:10.1159/000126365

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

His-dTrp-Ala-Trp-dPhe, Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 µg/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 µg/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexa-methasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while dexamethasone did not affect the GH responses to GHRH, highlighting a differential regulation of these hormones on somatotroph responsiveness to these peptide

ISSN:0028-3835    

DOI:10.1159/000126366

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

While interleukin-1 (IL-1) is intimately involved in locally modulating the acute inflammatory response, it is also able to influence processes at remote sites, i.e., in an endocrine manner. While there is as yet little evidence that IL-1 can cross the blood-brain barrier, many effects such as fever, increased slow-wave sleep, anorexia and the modulation of neuroendocrine function suggest an action of circulating IL-1 at regulatory sites within the hypothalamus. However, there is accumulating evidence for IL-1 originating within the central nervous system (CNS), and it is currently unclear as to whether the neurally mediated manifestations of the acute inflammatory response are due to activation of central or peripheral (circulating) IL-1. In this study we have characterized the release of IL-1 from rat hypothalamic explants, and we have investigated the effects of putative modulators of IL-1 release, lipopolysaccharide (LPS) and the prostaglandins E2 (PGE2) and F2α (PGF2α). After 1 h of incubation, IL-1-like activity in hypothalamic supernatants ranged between 175 and 2,304 munits/mg of protein; this was substantially inhibited by the addition to the bioassay system of antibodies (1:200) against IL-1α, but not against IL-1β. LPS and PGE2 significantly stimulated IL-1 release at 100 and 1 ng/ml respectively, whereas PGF2α had no effect in the range of doses tested. It is therefore concluded that the control of hypothalamic IL-1 release may be investigated by means of acute rat hypothalamic explants. Furthermore, both LPS and PGE2 can stimulate IL-1 release in this model, although no clear dose-response relationship could be discerned. Taking into account previous studies which have shown that IL-1 may specifically stimulate the release of hypothalamic PGE2, these data suggest that (1) PGE2 may mediate communication between circulating and CNS-derived IL-1, and (2) the effects of LPS on neuroendocrine function may occur, at least in part, independent of circulating

ISSN:0028-3835    

DOI:10.1159/000126367

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Previous studies from our laboratory have established an interaction between central nervous system nicotinic cholinergic systems and glucocorticoid hormones. When mice are treated for 1 week with exogenous corticosterone (CORT) they become insensitive to the behavioral and physiological actions of nicotine and also have a reduction in brain α-bungarotoxin (BTX) receptor binding. In the present study, mice were treated with high stress levels of CORT and nicotinic receptor binding was measured using quantitative autoradiographic methods. L-[3H]-nicotine and α-[125I]-bungarotoxin were used to label both high- and low-affinity nicotinic sites. Chronic CORT administration reduced BTX binding in 77 of 115 (67.0%) brain regions examined. In general, forebrain regions were more sensitive to this regulation than were more posterior brain regions. Hippocampal and hypothalamic regions were particularly susceptible, with binding in treated animals being reduced by up to 80% in some nuclei. L-[3H]-nicotine sites were not as sensitive to CORT regulation as binding was significantly reduced in only 7 of the 83 (8.4%) regions measured. Regions affected were restricted to the thalamus and septum. The mechanism by which CORT reduces brain nicotinic cholinergic receptor binding is unknown and may or may not be dependent on CNS glucocorticoid receptor

ISSN:0028-3835    

DOI:10.1159/000126368

出版商:S. Karger AG    

年代:1993

数据来源: Karger